Our main interest centers around the mechanism of DNA replication and recombination, their interrelation and the interaction of participating components. How is phage T4 DNA replication initiated? Is (at least) the first replication of the origin region different from replication of the remainder of the chromosome? By using appropriate phage and/or host mutants we want to investigate the role of polymerase I of E. coli in initiation or other replication of T4 and the interaction of phage or host components with this enzyme. Furthermore, we want to test by physical characterization, by DNA-DNA hybridization and by transformation, whether the DNA of the origin region is at first synthesized from one or from both parental strands. In what respect is this DNA similar to or different from Okazaki pieces? What is the role of genetic recombination in T4 DNA replication? Is T4 replication unidirectional and recombination is required for replication of the DNA at the anticlockwise side of the origin? Or is recombination required to initiate bidirectional replication? We want to answer these questions by a combination of electron microscopy and transformation with replication DNA, using appropriate phage or host mutants. Single exchange and double exchange recombination appear to occur with about equal frequencies near chromosomal ends of T4 (as well as in gene conversion of eukaryotes). We want to test, (aided by computer analysis) wether either or both of these patterns are reciprocal and whether certain recombination or replication deficient mutants differentially effect single and double exchange recombination. Finally, we want to test by using appropriate mutants and semi-in- vitro membrane systems which components participating in DNA replication and recombination of different systems are interchangeable. We will first test components from uninfected and T4 infected E. coli or other bacteria and hope to extend these studies to eukaryotic components, particularly from tissue cultures.